MedPath

Efficacy and Safety Study of Intravenous Progesterone in Patients With Severe Traumatic Brain Injury

Phase 3
Completed
Conditions
Brain Injuries
Interventions
Drug: Lipid emulsion without progesterone
Registration Number
NCT01143064
Lead Sponsor
BHR Pharma, LLC
Brief Summary

The SyNAPSe trial will study if giving intravenous (i.v.) progesterone within 8 hours of the injury for a total of 120 hours to severe traumatic brain injury patients improves their recovery.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1195
Inclusion Criteria
  1. Male or female patients between the age of 16 and 70 years, inclusive
  2. Weight from 45 to 135 kg, inclusive
  3. Sustained a closed head trauma no more than 8 hours before start of study drug infusion
  4. TBI diagnosed by history and clinical examination
  5. Post-resuscitation Glasgow Coma Scale (GCS) score between 3 to 8, inclusive
  6. At least one reactive pupil (pinpoint pupils due to opioid pain treatment are considered reactive)
  7. Evidence of TBI confirmed by abnormalities consistent with trauma on CT scan upon admission (diffuse injury II-IV, evacuated and non-evacuated mass lesion, Marshall's CT Classification)
  8. Indication for ICP monitoring
Exclusion Criteria
  1. Life expectancy of less than 24 hours as determined by the Investigator
  2. Prolonged and/or uncorrectable hypoxia (Pa02< 60 mmHg) or hypotension (systolic blood pressure < 90 mmHg) at the time of randomization
  3. Any spinal cord injury
  4. Pregnancy
  5. Penetrating head injury
  6. Bilaterally fixed dilated pupils at the time of randomization
  7. Coma suspected to be primarily due to other causes (e.g. alcohol)
  8. Pure epidural hematoma
  9. Preexisting clinically significant disease or chronic condition that can be ascertained at the time of admission and could affect functional outcome
  10. Severe cardiac or hemodynamic instability prior to randomization
  11. Known treatment with another investigational drug therapy or procedure within 30 days of injury
  12. A history of allergic reaction to progesterone and related drugs or any of the components of the infusion
  13. Any disease, in the opinion of the Investigator, that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
  14. Patients who, in the opinion of the Investigator, would not be able or willing to comply with the protocol through the final visit (6 months post-injury)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ProgesteroneProgesterone-
Lipid emulsion without progestroneLipid emulsion without progesterone-
Primary Outcome Measures
NameTimeMethod
Glasgow Outcome Scale (GOS)6 months

The GOS assesses mortality and disability in traumatic brain injury (TBI) patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State or Dead.

Secondary Outcome Measures
NameTimeMethod
Mortality at Month 11 month post injury

The mortality rate at one month will be compared between the two treatment groups.

Mortality at Month 66 months post injury

The mortality rate at six months will be compared between the two treatment groups.

Glasgow Outcome Scale at 3 MonthsMonth 3

The GOS assesses the mortality and disability in traumatic brain injury patients according to the designation: Good Recovery, Moderate Disability, Severe Disability, Vegetative State, or Dead.

Glasgow Outcome Scale - Extended (GOS-E)3 months and 6 months post injury

The GOS-E assessment of mortality and disability in TBI patients extends the original five GOS categories of functional outcome to eight categories:

* Dead

* Vegetative State

* Lower Severe Disability

* Upper Severe Disability

* Lower Moderate Disability

* Upper Moderate Disability

* Lower Good Recovery

* Upper Good Recovery

Short Form (36) Health Survey (SF-36)3 months and 6 months post injury

The Short Form (36) Health Survey (SF-36) is a validated survey of patient health consisting of eight scaled scores which are the weighted sums of the questions in their section. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, role physical, role emotional, role mental and mental health. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The 8 scales can also be further summarized to provide a summary score for physical health and a summary score for mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

Potentially Clinically Important On-Treatment Cerebral Perfusion Pressure (CPP) and Summary of Maximum Therapy Therapeutic Intensity Level (TIL)Admission through post-infusion Day 6

Cerebral Perfusion Pressure (CPP) levels are presented according to clinically significant cut-off values. CPP was calculated from intracranial pressures and mean arterial pressures measured from Day through Day 6 after initiation of study medication, if an ICP monitor was in place. Specific therapies received during Days 1-6 are summarized according to the Therapeutic Intensity Level (TIL) by treatment group, as maximum level of therapy administered to the subject.

Trial Locations

Locations (156)

University of South Alabama Medical Center

🇺🇸

Mobile, Alabama, United States

LAC+USC Medical Center

🇺🇸

Los Angeles, California, United States

University of California San Diego Medical Center

🇺🇸

San Diego, California, United States

Denver Health Medical Center

🇺🇸

Denver, Colorado, United States

Christiana Care Health System Hospital

🇺🇸

Newark, Delaware, United States

Delray Medical Center

🇺🇸

Delray Beach, Florida, United States

Tallahassee Memorial Healthcare

🇺🇸

Tallahassee, Florida, United States

Tampa General Hospital

🇺🇸

Tampa, Florida, United States

Saint Alphonsus Regional Medical Center

🇺🇸

Boise, Idaho, United States

John H. Stroger Jr. Hospital of Cook County

🇺🇸

Chicago, Illinois, United States

Advocate Lutheran General Hospital

🇺🇸

Park Ridge, Illinois, United States

Saint John's Hospital

🇺🇸

Springfield, Illinois, United States

Wishard Health Services

🇺🇸

Indianapolis, Indiana, United States

Methodist Hospital

🇺🇸

Indianapolis, Indiana, United States

Mercy Medical Center

🇺🇸

Des Moines, Iowa, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

University of Louisville Hospital

🇺🇸

Louisville, Kentucky, United States

LSU Health - Shreveport

🇺🇸

Shreveport, Louisiana, United States

Eastern Maine Medical Center

🇺🇸

Bangor, Maine, United States

Maine Medical Center

🇺🇸

Portland, Maine, United States

Baystate Medical Center

🇺🇸

Springfield, Massachusetts, United States

University of Massachusetts Memorial Medical Center

🇺🇸

Worcester, Massachusetts, United States

Bronson Methodist Hospital

🇺🇸

Kalamazoo, Michigan, United States

St. Mary's of Michigan

🇺🇸

Saginaw, Michigan, United States

University of Missouri Health Care

🇺🇸

Columbia, Missouri, United States

Truman Medical Center Hospital Hill

🇺🇸

Kansas City, Missouri, United States

Lester E. Cox Memorial Hospital

🇺🇸

Springfield, Missouri, United States

The Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Robert Wood Johnson University Hospital

🇺🇸

New Brunswick, New Jersey, United States

Albany Medical Center Hospital

🇺🇸

Albany, New York, United States

Westchester Medical Center

🇺🇸

Valhalla, New York, United States

Mission Hospital

🇺🇸

Asheville, North Carolina, United States

Carolinas Medical Center

🇺🇸

Charlotte, North Carolina, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Wake Forest University-Baptist Medical Center

🇺🇸

Winston-Salem, North Carolina, United States

Summa Health System

🇺🇸

Akron, Ohio, United States

MetroHealth Medical Center

🇺🇸

Cleveland, Ohio, United States

Miami Valley Hospital

🇺🇸

Dayton, Ohio, United States

St. Elizabeth Health Center

🇺🇸

Youngstown, Ohio, United States

OU Medical Center

🇺🇸

Oklahoma City, Oklahoma, United States

Legacy Emanuel Hospital & Health Center

🇺🇸

Portland, Oregon, United States

Allegheny General Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

University of South Carolina School of Medicine

🇺🇸

Columbia, South Carolina, United States

Johnson City Medical Center

🇺🇸

Johnson City, Tennessee, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Texas Tech University Health Sciences Center

🇺🇸

El Paso, Texas, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

Marshall University Joan C. Edwards School of Medicine

🇺🇸

Huntington, West Virginia, United States

West Virginia University Hospital

🇺🇸

Morgantown, West Virginia, United States

University of Wisconsin Hospital and Clinics

🇺🇸

Madison, Wisconsin, United States

Hospital Francisco Lopez Lima

🇦🇷

General Roca, Rio Negro, Argentina

Hospital de Emergencias Clemente Alvarez (HECA)

🇦🇷

Rosario, Santa Fe, Argentina

Hospital Nacional "Profesor Alejandro Posadas"

🇦🇷

Buenos Aires, Argentina

Hospital Regional De Comodoro Rivadavia (HRCR)

🇦🇷

Comodoro Rivadavia, Argentina

Hospital Central de Mendoza

🇦🇷

Mendoza, Argentina

Hospital San Martin

🇦🇷

Paraná, Argentina

Hospital Dr. José Maria Cullen

🇦🇷

Santa Fé, Argentina

Medizinische Universität Graz

🇦🇹

Graz, Austria

Medizinische Universität Innsbruck

🇦🇹

Innsbruck, Austria

Unfallkrankenhaus Salzburg

🇦🇹

Salzburg, Austria

Landesklinikum Wiener Neustadt

🇦🇹

Vienna, Austria

ULB Erasme

🇧🇪

Brussels, Belgium

Ziekenhuis Oost-Limburg, Location Sint Jan

🇧🇪

Genk, Belgium

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

University Hospital of the Free University Brussels (UZ Brussel)

🇧🇪

Jette, Belgium

University Hospital Gasthuisberg

🇧🇪

Leuven, Belgium

Chengdu Military General Hospital

🇨🇳

Chengdu, China

The First Affiliated Hospital of Fujian Medical University

🇨🇳

Fuzhou, China

The 2nd Affiliated Hospital of Zhejiang University

🇨🇳

Hangzhou, China

The Second Hospital of Shandong University

🇨🇳

Jinan, China

Huashan Hospital of Fudan University

🇨🇳

Shanghai, China

Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

🇨🇳

Shanghai, China

General Hospital of Tianjin Medical University

🇨🇳

Tianjin, China

The Affiliated Hospital of Xuzhou Medical College

🇨🇳

Xuzhou, China

Fakultní nemocnice Brno Neurochirurgická klinika

🇨🇿

Brno, Czechia

Fakultní nemocnice u sv. Anny v Brnĕ, Neurochirurgická klinika

🇨🇿

Brno, Czechia

Fakultní Nemocnice Plzeň, Neurochirurgicé Oddĕlení

🇨🇿

Plzeň, Czechia

Fakultní nemocnice Kralovske Vinohrady

🇨🇿

Praha, Czechia

Tampere University Hospital

🇫🇮

Tampere, Finland

Groupe Hospitalier Pellegrin

🇫🇷

Bordeaux, France

Hôpital Pierre Wertheimer

🇫🇷

Bron, France

Centre Hospitalier Universitaire de Grenoble- Hópital Michallon

🇫🇷

La Tronche, France

CHRU de Lille- Hópital Roger Salengro

🇫🇷

Lille, France

Centre Hospitalier Universitaire de Limoges

🇫🇷

Limoges, France

Centre Hospitalier Universitaire Hôpital Nord

🇫🇷

Marseille, France

Hópital Central - CHU de Nancy

🇫🇷

Nancy, France

Groupe Hospitalier La Salpêtrière

🇫🇷

Paris, France

Charité - Universitätsmedizin Berlin

🇩🇪

Berlin, Germany

Klinikum der J.W. Goethe-Universität

🇩🇪

Frankfurt, Germany

Universitätsmedizin Göttingen

🇩🇪

Göttingen, Germany

Berufsgenossenschaftliche Kliniken

🇩🇪

Halle, Germany

Universitätsklinikum Hamburg-Eppendorf

🇩🇪

Hamburg, Germany

Universitätsklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Krankenhaus Merheim

🇩🇪

Köln, Germany

Universitätsklinikum Gießen und Marburg gGmbH

🇩🇪

Marburg, Germany

Klinikum Nürnberg

🇩🇪

Nürnberg, Germany

Niels-Stensen-Kliniken

🇩🇪

Osnabrück, Germany

Universitätsklinikum Ulm

🇩🇪

Ulm, Germany

Honvédelmi Minisztérium Állami Egészségügyi Központ

🇭🇺

Budapest, Hungary

Pécsi Tudományegyetem Általános Orvostudományi Kar

🇭🇺

Pécs, Hungary

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ

🇭🇺

Szeged, Hungary

Rambam Medical Center

🇮🇱

Haifa, Israel

Hadassah Medical Organization

🇮🇱

Jerusalem, Israel

Rabin Medical Center

🇮🇱

Petach-Tikva, Israel

Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Chaim Sheba Medical Center

🇮🇱

Tel-Hashomer, Israel

Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

🇮🇹

Milano, Italy

Fondazione San Raffaele del Monte Tabor

🇮🇹

Milano, Italy

Azienda Ospedaliera San Gerardo

🇮🇹

Monza, Italy

Azienda Ospedaliero Universitaria Maggiore della Caritá

🇮🇹

Novara, Italy

Azienda Ospedaliera San Camillo Forlanini

🇮🇹

Rome, Italy

Azienda Ospedaliero Universitaria Integrata di Verona

🇮🇹

Verona, Italy

Hospital Raja Permaisuri Bainun

🇲🇾

Ipoh, Malaysia

Hospital Kuala Lumpur

🇲🇾

Kuala Lumpur, Malaysia

University Malaya Medical Centre

🇲🇾

Kuala Lumpur, Malaysia

Hospital Tengku Ampuan Afzan

🇲🇾

Kuantan, Malaysia

Sarawak General Hospital

🇲🇾

Kuching, Malaysia

VU Medisch Centrum

🇳🇱

Amsterdam, Netherlands

Universitair Medisch Centrum Groningen

🇳🇱

Groningen, Netherlands

Spitalul Clinic Judetean de Urgenta Timisoara

🇷🇴

Timisoara, Romania

State Budget Educational Institution of Higher Professional Education "Kemerovskaya State Medical Academy of Federal Agency of Healthcare and Social Development"

🇷🇺

Kemerovo, Russian Federation

State Professional Institution of High Professional Education "Krasnoyarsk State Medical University named after Prof. V.F. Voyno-Yasenetsky of Ministry of Health and Social Development"

🇷🇺

Krasnoyarsk, Russian Federation

State Institution "Burdenko Neurosurgical Institute of RAMS"

🇷🇺

Moscow, Russian Federation

State Healthcare Facility "Murmansk Regional Clinical Hospital n.a. Bayandin"

🇷🇺

Murmansk, Russian Federation

Saint Petersburg Healthcare Institution "City Mariinsky Hospital"

🇷🇺

St. Petersburg, Russian Federation

State Institution of Health Care "Sverdlovsk Regional Clinical Hospital #1"

🇷🇺

Yekaterinburg, Russian Federation

National Neuroscience Institute

🇸🇬

Singapore, Singapore

National University Hospital

🇸🇬

Singapore, Singapore

Singapore General Hospital

🇸🇬

Singapore, Singapore

Hospital Universitario Germans Trias i Pujol

🇪🇸

Badalona, Barcelona, Spain

Hospital Parc Taulí

🇪🇸

Sabadell, Barcelona, Spain

Hospital General Universitario de Alicante

🇪🇸

Alicante, Spain

Hospital Universitario de Bellvitge

🇪🇸

Barcelona, Spain

Hospital Universitario Vall Hebrón

🇪🇸

Barcelona, Spain

Hospital Universitario de Girona Dr. Josep Trueta

🇪🇸

Girona, Spain

Hospital Universitario de Gran Canaria Dr. Negrín

🇪🇸

Las Palmas de Gran Canaria, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Universitari Son Espases

🇪🇸

Palma de Mallorca, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Hospital Clínico Universitario De Valencia

🇪🇸

Valencia, Spain

Hospital Universitari i Politecnic La Fé de Valencia

🇪🇸

Valencia, Spain

Taichung Veterans General Hospital

🇨🇳

Taichung, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Chiang Mai University

🇹🇭

Chiang Mai, Thailand

Faculty of Medicine, Prince of Songkla University

🇹🇭

Hat yai, Thailand

Khon Kaen Hospital

🇹🇭

Khon Kaen, Thailand

Royal Preston Hospital

🇬🇧

Fulwood, Preston, United Kingdom

Queen Elizabeth Hospital

🇬🇧

Birmingham, United Kingdom

University Hospital Coventry

🇬🇧

Coventry, United Kingdom

Leeds Teaching Hospitals NHS, Leeds General Infirmary

🇬🇧

Leeds, United Kingdom

The Royal London Hospital

🇬🇧

London, United Kingdom

The James Cook University Hospital

🇬🇧

Middlesbrough, United Kingdom

Southampton University Hospital

🇬🇧

Southampton, United Kingdom

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